1. Field of the Invention
This invention relates to magaldrate antacid powder compositions which are rehydratable to form pharmaceutically elegant high and low concentration, pourable, aqueous antacid suspension dosage forms for oral administration and to methods for their preparation and use.
2. Description of the Antacid Art
Antacids are widely used in the treatment of gastrointestinal disorders. Their effectiveness in promoting the healing of gastric and duodenal ulcers has been well documented. Essentially, antacids exert their positive effects by neutralizing the gastric acid secreted in the stomach. When the pH of stomach contents is raised above 3, most gastric acid is neutralized and the proteolytic activity of pepsin is inhibited. The recent elevation of antacids to a major therapeutic role, particularly in ulcer therapy, rather than a merely palliative role, has emphasized the importance of providing antacid products featuring a high neutralization (and buffer) capacity as well as a rapid rate of gastric acid neutralization. These features, particularly that of rapid rate of neutralization to the neutralization capacity of the antacid, define the more effective antacid in vivo since it is less likely that non-reacted antacids will be removed by normal gastric emptying.
Most antacids are available in both liquid and solid dosage forms. The liquid antacids, as aqueous suspensions, are, generally, more effective than the same antacids in solid dosage forms and are more commonly prescribed in the hospital. The greater effectiveness of liquid antacids is partially due to the large surface area available in liquid suspensions to react with gastric acid and partially due to the great amount of colloidal particles in aqueous suspensions which can more easily reach the affected area where treatment is needed. Moreover, aqueous suspensions of not previously dried antacids are more reactive than dry or solid antacids.
While liquid antacids possess these advantages, the same require administration of relatively large volumes of liquid suspension. The ingestion of such large volumes is inconvenient, however, making the normal problem of assuring patient compliance outside the hospital environment even more difficult. Since high dose regimens of liquid antacid have recently been shown to be effective both in promoting the healing of duodenal ulcers and in preventing the acute upper gastrointestinal bleeding in critically ill patients, the use of regular liquid antacid suspensions with the usual antacid content in the 6-12 percent range has become even more impractical for such therapeutic indications.
The most widely used antacids can be described as mineral type, insoluble inorganic salts that are hydrated, possess colloidal properties, and contain, for example, aluminum, magnesium, bismuth and the like. Compounds of the described mineral variety in their freshly prepared, hydrated form and in suspensions therefrom provide some of the characteristics desired in an antacid. To provide liquid antacids with a high neutralization capacity it is necessary to increase the solids concentration of the antacid components. Such increases in concentration, however, are accompanied at higher levels with exponential increases in viscosity, a loss in colloidal properties and a loss of fluidity or mobility. Even when fluidity is initially maintained or achieved, further requirements of pharmaceutically acceptable aqueous antacid suspensions call for a smooth (non-gritty) mouth feel and maintenance of a gel structure for both suspendibility and resuspendibility. In general, resuspendible, aqueous antacid suspensions are typically partially de-flocculated products which contain a deflocculant and suspending agent to arrest or control further agglomeration or flocculation and settling. In the absence of a deflocculant and suspending agent type additive, the antacid in a suspension forms a hard cake or a gel structure which can no longer be resuspended with its original desirable characteristics.
Thus deflocculants and suspending agents have been frequently included in the formulation of aqueous antacid suspensions containing solid antacid concentrations in the range of about 6 to 12 percent to prevent caking. With the growing interest in providing antacid suspension dosage forms with a greater acid neutralizing capacity, means were sought to provide highly concentrated but fluid systems.
Although it has been reported that liquid antacids take effect faster and provide longer duration than the same antacids in solid dosage form, some disadvantages also exist in the preparation of liquid antacids. For example, high pH value (8-10) of the antacid suspension makes the microbial preservation of this product a difficult task. Most preservatives which are suitable for ingestion are not stable or effective in this pH range. In aging, some antacid gels could change from an active amorphous form to a less active crystalline form. As liquid antacids contain about 80-90% of water, they are not only inconvenient to use but also sensitive to both microbial contamination and temperature change. The cost of package, shipment and storage is more expensive for liquid than solid antacids. Therefore, it would be useful to develop an antacid powder which can be reversibly converted to its original colloidal state when wetted with water.
When magaldrate is precipitated by adding the magnesium salt to the alkali aluminate solution, it is a white gel containing 6-15% solids. The spray dried powder of this gel is not rehydratable to a smooth suspension. When wetted with water, the powder remains intact and can not go back to its colloidal state. This powder appears less effective and tastes gritty. Therefore, there is a need in the art for a totally rehydratable magaldrate powder which can be easily formulated, shipped to a distant facility, stored for a period of time and reconstituted to a colloidal suspension when it is needed.
Copending application Ser. No. 661,648, filed Oct. 17, 1984 in the names of Wu and Reuter and entitled "Fluidized Magaldrate Suspension", herein incorporated by reference in its entirety, describes and claims an aqueous antacid composition characterized in providing a fluid, resuspendible, pharmaceutically elegant antacid suspension with high antacid capacity comprising precipitated and undried magaldrate gel and a fluidizing amount of a combination of an aluminum hydroxide gel having colloidal properties as a first fluidizer and a second fluidizer selected from at least one of the group consisting of citric acid and a pharmaceutically acceptable citrate ion source.
It has now been found that the composition disclosed and claimed in copending application Ser. No. 661,648 after addition of a polyhydric alcohol can be dehydrated to form a dry rehydratable magaldrate composition.
It is therefore an object of this invention to provide rehydratable magaldrate compositions in solid powder form which when admixed with water form aqueous antacid suspensions with high antacid capacity and good mouth feel characteristics.
Another object of this invention is to provide rehydratable magaldrate compositions in solid powder form which when admixed with water form aqueous antacid suspensions with high antacid capacity and which retain, at high concentrations, the desirable qualities of rapid acid neutralization and reliably uniform reaction in acidic solutions.
A further object of the invention is to provide high antacid capacity, rehydratable magaldrate compositions in solid powder form, which when admixed with water form suspensions with good fluidity, pourability and suspension characteristics and which further provides full resuspendibility under the typical shelf life conditions for a commercial aqueous antacid suspension, and which can also be formulated into chewable tablets with reduced grittiness when ingested.